A number of pathological conditions exist in the mammalian respiratory tract which have been attribued to altered ciliary function or altered muco-ciliary clearance, i.e., Kartegener's Syndrome, immotile cilia syndrome, cystic fibrosis and chronic bronchitis. It is difficult to study these diseases when it is not understood how normal ciliated cells move a layer of mucous by beating its cilia and how altered function may interrupt such activity and induce disease. The current hypothesis on ciliary beat only reflects activity stemming from the ciliary shaft. This proposal is based upon the hypothesis that the basal body and microtubule/microfilament interactions in the apical cytoplasm play an integral role in ciliar beat. As an initial step, we plan to critically examine normal structure of the basal body, rootlet and interbasal body apparatus in the ciliated cells of the respiratory tract and to determine how they may differ from other systems which have been studied more thoroughly, i.e., gill cilia. Following a careful study of the 3-dimensional organization of the apical cytoplasm, the ciliated cell will be separated biochemically into its components and evaluated for its protein content, particularly those associated with mechanochemical properties, i.e., actin, myosin and tropomyosin. Purified proteins will be used as immunogens to produce specific antibodies which will then be employed as molecular probes to determine ultrastructurally which protein corresponds to each component in a 3-dimensional model. Ciliogenesis will be studied to reveal how the basal bodies integrate into the pre-existing filamentous network for a better understanding of the structural relationships observed in the fully matured cell. Finally, a number of drugs will be employed which affect microtubule and microfilament integrity to verify how these structures are associated with basal bodies and their role in supporting ciliary beat.